Mycolactone is a macrolide secreted by Mycobacterium ulcerans. Experimental evidence suggests that mycolactone plays a prominent role in the pathogenesis of Buruli ulcer by causing both tissue destruction and immunosuppression. To understand the cell biology of mycolactone activity, we have synthesized the fluorescent mycolactone derivativebodipymycolactone. Although derivatization resulted in a ...

Plasmid R1 inhibits growth of bacteria by synthesizing an inhibitor of cell proliferation, Kid, and a neutralizing antidote, Kis, which binds tightly to the toxin. Here we report that this toxin and antidote, which have evolved to function in bacteria, also function efficiently in a wide range of eukaryotes. Kid ...

Anaplastic thyroid carcinomas (ATCs) are highly aggressive, extremely lethal human cancers with poor therapeutic response. Chemokines are a superfamily of small cytokine-like proteins that induce, through their interaction with G protein-coupled receptors, cytoskeletal rearrangement, firm adhesion to endothelial cells, and directional migration. In this study, we characterized the expression of ...

Ricin is a naturally occurring toxin derived from the beans of the castor oil plant Ricinus communis. It is considered a potential chemical weapon. Ricin binds to cell surface carbohydrates, is internalised then causes cell death by inhibiting protein synthesis. Oral absorption is poor and absorption through intact skin most ...

Arcobacter has been shown to be present in numerous different sources, including poultry, water, and humans exhibiting gastroenteritis. The production of a cytolethal distending toxin (CDT) has been documented in Campylobacter, Helicobacter, and other species. The polymerase chain reaction was used to screen Arcobacter isolates from poultry, cattle, irrigation water, ...

This is the first study reporting the inactivation of a member of the mouse gene family of toxin-related ecto-ADP-ribosyltransferases (ARTs). Transfer of the ADP-ribose moiety from NAD onto extracellular arginine residues on T-cell membrane proteins is mediated by glycosylphosphatidylinositol-linked cell surface ARTs. Exposure of T cells to ecto-NAD blocks T-cell ...

Many plant and bacterial toxins act upon cytosolic targets and must therefore penetrate a membrane barrier to function. One such class of toxins enters the cytosol after delivery to the endoplasmic reticulum (ER). These proteins, which include cholera toxin (CT), Pseudomonas aeruginosa exotoxin A (ETA), and ricin, move from the ...

The anthrax edema toxin comprises two proteins: protective antigen and edema factor. Anthrax protective antigen binds to the receptors on the surface of target cells and facilitates the entry of edema factor into these target cells. Edema factor (EF) is an adenylate cyclase that catalyzes the synthesis of cyclic AMP ...

We tested the significance of a population of lumbar spinothalamic cells for male sexual behavior in rats. These cells are positioned to relay ejaculation-related signals from reproductive organs to the brain, and they express neurokinin-1 receptors. Ablation of these neurons by the selective toxin SSP-saporin resulted in a complete disruption ...

In this report we demonstrated that cellular prion protein is strictly associated with gangliosides in microdomains of neural and lymphocytic cells. We preliminarily investigated the protein distribution on the plasma membrane of human neuroblastoma cells, revealing the presence of large clusters. In order to evaluate its possible role in tyrosine ...

Since the initial discovery of the yeast killer system almost 40 years ago, intensive studies have substantially strengthened our knowledge in many areas of biology and provided deeper insights into basic aspects of eukaryotic cell biology as well as into virus-host cell interactions and general yeast virology. Analysis of killer ...

The periodontal pathogen Actinobacillus actinomycetemcomitans produces cytolethal distending toxin (CDT), a complex multicomponent toxin that arrests the growth of many types of eukaryotic cell. The kinetics of the effects of CDT-containing extracts, from an invasive strain of this bacterium, were examined on epithelial-like cells routinely used in invasion studies. Both ...

Clostridium botulinum C2 enterotoxin consists of two unlinked proteins designated as C2II, which recognizes a cell-surface glycoprotein and translocates an ADP-ribosyltransferase, C2I, into the cytosol of a targeted cell. Fluorescence-activated cytometry was used to study the cellular interactions of Alexa488-labeled C2I (C2I-A488) and proteolytically activated C2II (C2IIa-A488). The binding of ...

A variety of extracellular ligands and pathogens interact with raft domains in the plasma membrane of eukaryotic cells. In this study, we examined the role of lipid rafts and raft-associated glycosylphosphatidylinositol (GPI)-anchored proteins in the process by which Helicobacter pylori vacuolating toxin (VacA) intoxicates cells. We first investigated whether GPI-anchored ...

The development of suicide gene therapy with gene products that are directly toxic to cells, such as the A subunit of diphtheria toxin (DT-A), has been hampered by the difficulty of engineering recombinant viruses. DT-A is a strong inhibitor of protein synthesis that acts by ADP-ribosylating elongation factor 2, and ...

Lysophosphatidic acid (LPA) is a naturally occurring phospholipid that activates a variety of biological activities including cell proliferation. Three mammalian LPA receptor (LPAr) subtypes have been identified by molecular cloning, named lp(A1), lp(A2) and lp(A3), that are coupled to heterotrimeric G-proteins for signal transduction. The LPAr are endogenously expressed in ...

Destruxins (DTXs) are cyclic peptide toxins secreted by the entomopathogenic fungus Metarhizium anisopliae var. anisopliae. The effects of DTX E, the most active compound of this family on haemocytes, the immunocompetent insect cells, and on the dynamics and efficacy of the multicellular defense of insect hosts have been investigated. Ultrastructural ...

We have shown that urea-extracted cell wall of entomopathogenic Bacillus sphaericus 2297 and some other strains is a potent larvicide against Culex pipiens mosquitoes, with 50% lethal concentrations comparable to that of the well-known B. sphaericus binary toxin, with which it acts synergistically. The wall toxicity develops in B. sphaericus ...

Several strains of Vibrio cholerae secrete a haemolytic toxin of 63 kDa, termed V. cholerae cytolysin (VCC). This toxin causes extensive vacuolation and death of cells in culture and forms an anion-selective channel in planar lipid bilayers and in cells. Here, we identify inhibitors of the VCC anion channel and ...

A Cytosensor microphysiometer, which measures extracellular acidification rate (ECAR), was used to study the early metabolic activation by organic dust from a swine confinement building in a human airway epithelial cell line, A549. The dust is known to cause an intense airway inflammatory reaction following inhalation in vivo and cytokine ...

The nucleotide sequence deduced from the amino acid sequence of the scorpion insectotoxin AaIT was chemically synthesized and was expressed in Escherichia coli. The authenticity of this in vitro expressed peptide was confirmed by N-terminal peptide sequencing. Two groups of bioassays, artificial diet incorporation assay and contact insecticidal effect assay, ...

Squamous cell carcinoma of the head and neck (SCCHN) is characterized by a high proliferation index and marked propensity for local invasion resulting in poor prognosis for these patients. To develop tumor-targeted novel therapeutic agents, here we demonstrate that SCCHN cell lines express receptors for an immune regulatory cytokine, interleukin ...

The alpha 7 nicotinic acetylcholine receptor (nAChR) subunit can be assembled to form a homomeric-pentamer with high permeability to calcium. Although the expression of the alpha 7-nAChR has been demonstrated throughout the CNS, the neurochemical phenotype of neurons expressing alpha 7 remains to a large extent unknown. Using an antibody ...

Aflatoxin B1 is a mycotoxin produced by Aspergillus flavus and Aspergillus parasiticum, which may be present as a food contaminant. It is known to cause acute toxic effects and act as a carcinogenic agent. The carcinogenic action has been related to its ability to form unstable adducts with DNA, which ...

The studies on the inhibitory effect exerted by Cholera Toxin (CT) on cell growth and proliferation indicate a remarkable heterogeneity of cell response suggesting that the inhibition represents the final event of many different ways or mechanisms. After CT binding, cAMP accumulation may not occur (as in L1210 leukemia cells) ...

Clostridium perfringens iota-toxin is a binary toxin consisting of two individual proteins, the binding component (Ib) and the enzyme component (Ia). Wild-type Ib bound to Vero cells at 4 and 37 degrees C and formed oligomers at 37 degrees C but not at 4 degrees C. The Ib-induced K(+) release ...

Membrane guanylate cyclase C (GC-C) is the receptor for guanylin, uroguanylin, and heat-stable enterotoxin (STa) in the intestine. GC-C-deficient mice show resistance to STa in intestine but saluretic and diuretic effects of uroguanylin and STa are not disturbed. Here we describe the cellular effects of these peptides using immortalized human ...

Brefeldin A (BFA) perturbs the organization of the Golgi apparatus, such that Golgi stack components are fused with the endoplasmic reticulum (ER) and separated from the trans-Golgi network. In many cell types, BFA blocks the secretion of macromolecules but still allows the action of Golgi enzymes in the ER. Treatment ...

An ability to deliver macromolecules into the intracellular compartments of mammalian cells offers enormous potential for development of new therapeutics directed against intracellular targets. Unfortunately, most peptides or proteins are too large to enter the cell cytosol unaided, and any uptake that does occur primarily results in their entry into ...

In this study we show that the ganglioside content and pattern of human skin fibroblasts change along the process of cell subculture progression by varying the cell density. GM3, GD3 and GD1a were components of the total cell ganglioside mixtures extracted from cells, but GD1a was in all the extracts ...

BACKGROUND/PURPOSE: Despite aggressive treatment with surgery, chemotherapy, and radiotherapy, the prognosis for many children with neuroblastoma remains poor. Targeted toxins represent novel cancer therapeutics designed to selectively target and kill cancer cells. The authors have developed a novel fusion toxin, DT5F11, consisting of truncated diphtheria toxin (DT(A)) linked to a ...

The coevolution of bacterial pathogens and their hosts has contributed to the development of very complex and sophisticated functional pathogen--host interfaces. Thus, well-adapted pathogens have evolved a variety of strategies to manipulate host cell functions precisely. For example, a group of unrelated Gram-negative pathogenic bacteria have evolved a toxin, known ...

Recent reports have shown that protein A of Staphylococcus aureus (SpA) is a specific toxin for B cells by virtue of specific binding interactions with conserved sites on the V(H) region of the B-cell antigen receptor. The structural basis for these Fab-binding interactions has recently been revealed in crystallographic analyses, ...

Inhibition of the binding of [3H]ponasterone A ([3H]PoA) by ecdysone agonists including diacylhydrazines such as RH-5849, tebufenozide (RH-5992) and methoxyfenozide (RH-2485) was examined in intact Drosophila Kc cells. The reciprocal logarithm of the concentration at which there is 50% inhibition of [3H]PoA binding, pIC(50) (M), was determined as the binding ...

Although many of the problems associated with the use of conventional lesion techniques (aspiration, electrolytic, radiofrequency) can be avoided by employing focal injections of excitotoxins, experience gained over the past 12 years has shown that considerable care must be exercised with this newer method, to limit the cell loss to ...

The anthrax toxin comprises three proteins. When they work together, they can kill humans, especially after spores of the bacteria have been inhaled. One anthrax protein, called protective antigen (PA), chaperones the two other toxins into human or animal cells and shields them from the body's immune system. The second, ...

A direct effect of uraemic toxins in promoting progression of chronic renal disease has not been established. In this study, we investigated the toxic effects of organic anions which characteristically appeared in the patients with progressive renal disease on renal proximal tubular cells expressing human organic anion transporter (hOAT) 1. ...

Streptolysin O (SLO), archetype of a cholesterol-binding bacterial cytolysin, forms large pores in the plasma membrane of mammalian cells. We have recently reported that when a limited number of pores are generated in a cell, they can be sealed in a Ca++-dependent process. Here, we show that resealing is followed ...

Interleukin 13 receptor (IL-13R)-targeted cytotoxin, IL13-PE38QQR, composed of IL-13 and a mutated form of Pseudomonas exotoxin (PE), is found to be highly and specifically cytotoxic to human solid cancer cell lines. However, the mechanism of tumor cell death mediated by IL-13 toxin is still not known. To elucidate the mechanism, ...